Hepatobiliary UWorld: Path, Physio, Pharm Flashcards
What is the marker for HCC?
alpha-fetoprotein (AFP)
3 major etiologies of hepatocellular carcinoma
Viral infection with hep B or C
Chronic alcoholism
Food contaminants (aflotoxin)
Cirrhosis is not required for dx but seems to be a major contributor
Hemtemesis, palpable spleen, esophageal varices, portal hypertension, no abnormalities on liver biopsy. Dx?
Portal vein thrombosis. (Long-term alcohol would show cirrhosis on biopsy)
Crigler-naijar syndrome
Autosomal recessive absence of liver conjugation enzymes. Causes unconjugated hyperbilirubinemia. UCB cannot be excreted, so builds up in tissues like the brain, causes bilirubin encephalopathy.
Kernicterus
Bilirubin encephalopathy, potentially fatal condition with severe jaundice and neurological impairment. UCB builds up in basal ganglia
Dubin-Johnson syndrome
Autosomal recessive absence of biliary transport protein, defective liver excretion. Causes conjugated bilirubinemia, benign except for black liver.
Rotor syndrome
Like Dubin-Johnson but milder: defect of biliary transport protein, defective liver excretion. Causes conjugated bilirubinemia, benign and NO black liver
Lab tests that assess liver function
prothrombin time, bilirubin, albumin, cholesterol
Lab tests that assess structural/cellular integrity of liver
Transaminases (AST, ALT)
Lab tests that assess biliary tract
Alkaline phosphatase (nonspecific, found in lots of tissues), gamma glutamyl transferase (more specific)
Elevated alkaline phosphatase: what is next thing to check?
gamma glutamyl transpeptidase
What is acute cholecystitis? Main cause?
Acute inflammation of gallbladder, initiated by obstruction of gallbladder neck or cystic duct. This is the major complication of cholelithiasis
Gilbert syndrome
Mild familial decrease in UDG conjugation enzyme. Only clinical sign is jaundice in times of stress: fasting, fever, hemolysis, fatigue, exertion.
Treatment of acetominophen overdose, mechanism
N-acetyl cysteine, binds toxic metabolite and provides sulfhydryl groups to sulfonate and metabolize
Antidote in iron poisoning
Deferoxamine
“Serum sickness”, malaise, fever, skin rash, pruritis, lymphadenopathy, joint pain. Followed by anorexia, jaundice, RUQ pain.
Acute viral Hep B
Acute viral hepatitis labs
Significant elevations in ALT and AST (ALT>AST), rise in bilirubin and alk phos
What tests do you need to do for pt on statins
LFTs
Most common malignant hepatic lesion
Metastasis
Black pigment stones
Gallstones seen in chronic extravascular hemolysis. Usually small, spiculated, crumbly, and radioopque. Form when UCB precipitates as calcium bilirubinate.
Significant risk factor for cholesterol stones, black pigment stones, brown pigment stones
Cholesterol: Obesity, Crohn, CF, age, estrogen, drugs
Black: hemolysis
Brown: infection
Mechanism of damage in hepatic steatosis
Increased activity of dehydrogenase enzymes –> increased NADH –> decreased fatty acid oxidation.
Possible outcomes of hep B infection
- Acute hepatitis with complete resolution (95%)
- Chronic hepatitis (with or without cirrhosis)
- Fulminant hepatitis with massive liver necrosis
HIDA scan
Nadionuclide scan, used for dx of acute cholecystitis. If you don’t see gall bladder on the scan, the cystic duct is obstructed and it is a positive test result.
Gross and histo findings in Dubin-Johnson syndrome
Gross: black liver
Histo: normal, may see dense pigment with epinephrine metabolites within lysosomes
Middle aged woman, insidious onset, pruritis, fatigue, hepatosplenomegaly, jaundice, steatorrhea, portal htn osteopenia. Elevated alk phos and cholesterol. Serum anti mitochondrial antibodies. Maybe associated with autoimmune disease
Primary biliary cirrhosis
Primary biliary cirrhosis pathophys
Autoimmune destruction of intrahepatic bile ducts and cholestatis.
Primary biliary cirrhosis: associations
Sjogren syndrome, CREST, Raynaud’s, RA, celiac, thyroid disease
Hepatitis B: risk of hepatocellular carcinoma?
Increased. Virus integrates DNA into host genome
Main mechanism of excess copper removal (healthy)
In liver, incorporated into ceruloplasmin. Some goes into plasma (most of circulating copper), some is excreted via bile, stool.
Mechanism of damage in viral heptitis
Infected hepatocytes display viral antigens on MHC 1, and CD8 T-cells destroy.
Neuro symptoms, elevated transaminases, decreased serum ceruloplasmin
Wilson’s disease. Tx is penicillamine
Acute acalculous cholecystitis
Acute inflammation of gallbladder in absence of gall stones. Secondary to stasis and ischemia.
Seen in hospitalized pts with: sepsis, immunosuppression, trauma, burns, DM, infxn, surgery.
Middle aged female with long history of pruritis and fatigue who develops pale stool and xanthelasma. Classic picture of
primary biliary cirrhosis
Pt with HBV develops hepatocellular carcinoma. What is the trigger?
Integration of viral DNA into host genome: activates insulin-like growth factors and proliferation, and suppresses p53.
Pathogenesis of biliary atresia
Complete obstruction of extrahepatic bile ducts, due to failure to form or destruction of biliary tree
Presentation, labs, liver biopsy of biliary atresia
P: Jaundice, dark urine, firm enlarged liver in first 3 months of life
L: Increased direct bilirubin (CB), alk phos, gamma glutamyltransferase
B: Intrahepatic duct proliferation, portal tract edema and fibrosis, paranchymal fibrosis
Where does copper deposit in Wilson’s?
Cornea (Kayser-Fleischer rings), basal ganglia (neuro symptoms)
Hepatic encephalopathy
Reversible decline in neurologic function precipitated by hepatic damage. Often set off by stressor. Failure of liver to metabolize waste products –> increased ammonia in circulation.
Hemochromatosis is a disease of
intestinal absorption of iron. Loss of regulation of enterocytes –> too much absorption.
A1AT deficiency on liver biopsy
Red/pink PAS+ granules of unsecreted, polymerized A1AT in periportal hepatocytes
Increased estrogen in cirrhosis comes from? Causes?
Hyperestrinism is from liver’s inability to metabolize estrogens and increased sex hormone-binding globulin –> estrogen excess state.
Testicular atrophy, gynecomastia, spider angiomata
End stage liver disease - gross liver
Cirrhosis. Diffuse firosis, nodular parenchymal regeneration replaces lobular architecture.
Hemochromatosis causes iron overload in:
heart, pancreas, liver
Hep B: biopsy
Cytoplasm filled with spheres and tubules of HBsAg, fine granular eosinophilic “ground glass” appearance.
HBV vs HCV
B: Ballooning degeneration, hepatocyte necrosis, portal inflammation, ground glass cytoplasm appearance
C: Lymphoid aggregates within portal tracts, focal areas of macrovesicular steatosis
A 45 y/o Caucasian male has slow/incomplete gallbladder emptying in response to CCK. He is likely to develop:
biliary sludge
Aflatoxins cause
hepatocellular carcinoma via a p53 mutation
Administration methods to avoid first pass metabolism
IV, sublingual, rectal
Elderly female with waves of abdominal pain, nausea, vomiting. Air in biliary tree, hard mass with high cholesterol content in ileocecal valve
Gallstone ileus. Large gallstone erodes into intestinal lumen, fistula between gallbladder and intestine. Intermittent obstruction (waves of symptoms), eventually stuck in ileum.
What are the worst prognostic indicators in cirrhosis?
Prolonged PT, hypoalbuminemia, these are indicators of liver function
Note: AST, ALT are indicators of hepatocellular damage but not failure.
Isoniazid toxicity
Anti-TB, decreases synthesis of mycolic acids. Neurotoxicity, hepatotoxicity, transient increases in AST and ALT
INH Injures Neurons and Hepatocytes
21 y/o, Impaired balance, difficulty speaking, onset over a few months, elevated transaminases, no dugs or alcohol.
Wilson’s disease. Do slit lamp check
Fluid filled cavity in liver, fever chills and RUQ pain
Hepatic abscess. Can occur via s aureus seeding hematogenously, or enteric bacteria ascending biliary tract.
Pathogenesis of cholesterol gallstones
Increased cholesterol, decreased bile acids and phospholipids –> bile becomes supersaturated –> nucleation, aggregation promoted by mucus hypersecretion, calcium salts, hypomotility –> stone
3 drugs that increase risk for cholesterol gallstones
Fibrates (esp with bile acid resins), octreotide, ceftriaxone
How do fibrate cause cholesterol stones?
Suppression of 7a-hydroxylase activity reduces conversion to bile acids, excess secretion of cholesterol into bile
Cholestasis relation to osteomalacia?
Causes ADEK deficiency, so D deficiency is associated with osteomalacia (reduced bone density because of decreased mineralization)
Causes of cholestasis
- 2ndary to hepatocellular dysfunction
- Intrahepatic obstruction: drug induced, primary biliary cirrhosis, pregnancy, primary sclerosing cholangitis
- Extrahepatic obstruction: Choledocholithiasis, malignancy
First order vs zero order kinetics
First order: dose dependent, constant proportion metabolized
Zero order: dose independent, constant amount metabolized
When a drug reaches saturation, it switches to zero order
Most common benign liver tumor
Cavernous hemangioma
Cavernous hemangioma
Benign liver tumor. Consist of cavernous blood-filled vascular spaces lined by single epithelial layer. Do not biopsy due to risk for hemorrhage
Most likely outcome of acute Hep C infection
Stable chronic hepatitis
Progression to cirrhosis is a close second
What are brown pigment stones from?
Secondary to infection, which results in release of b-glucoronidase by injured hepatocytes and bacteria.
How does prolonged parenteral nutrition cause gallstones?
Decreased CCK release because of lack of enteral stimulation
Drug characteristics that allow for hepatic clearance into bile and stool
High lipophilicity, high volume of distribution
Inhaled anethetic toxicity
Hepatotoxicity: either transferase elevation and no symptoms, or severe fulminant hepatitis. Hypersensitivity reaction. Liver atrophy, elevated transferases, prolonged ptt, leukocytosis, eosinophilia. Widespread necrosis and inflammation. Histo like filminant viral.
Note: albumin is not decreased because this is acute event.
Hemochromatosis triad
skin hyperpigmentation, DM, pigment cirrhosis with hepatomegaly
“golden diabetes”
Most common cause of hydatid cysts
Tapeworm echinococcus granulosus. Aspiration of cyst is not advised due to risk of anaphylactic shock
Histo findings in acute viral hepatitis
Lymphocytic infiltrates, ballooning hepatocytes, hepatocyte necrosis, and apoptosis (with acidophilic apoptotic bodies)
Microscopy findings in Reye syndrome
microvesicular steatosis, small fat vacuoles in cytoplasm
Marker for evaluating cirrhotic pts for HCC
AFP
Ballooning degeneration
Viral hepatitis
Why do women present later with hemochromatosis?
Menstrual bleeding –> iron loss
Why is there increased incidence in gall stones in pregnancy and OCPs?
- Estrogen increases HMG-CoA reductase activity –> cholesterol hypersecretion
- Progesterone induces gall bladder hypomotility
Diffuse gallbladder calcification
Porcelain gallbladder, due to chronic cholecystitis, incidental finding. High rate of progression to gallbladder carcinoma
